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The spatial pattern and temporal sequence in which feather germs arise in the white Leghorn chick embryo.

Feather germs arise in a specific sequence and spatio-temporal pattern within each of 10 feather areas on the White Leghorn chick embryo. The time of feather germ initiation was determined by histological and gross macroscopic analyses. Protruding feather germs are sequentially visualized in the dorsal, thigh, breast, head, humoral, ventral, wing, eye, and external auditory meatus feather areas, respectively, from stage 31- to stage 39+ [V. Hamburger and H.L. Hamilton (1951) J. Morphol. 88, 49-92]. The rate at which successive feather tracts appear was found to differ for different feather areas and was not simply due to the size of a feather area. Feather germ histogenesis was examined in the dorsal, thigh, breast, ventral, wing, and tail feather areas. The stages of feather germ histogenesis, examined on the wing feather area, are similar to those previously described for the dorsal surface. Gross and histological analyses gave different times and temporal sequences of feather germ visualization. Some feather areas were readily visualized at the time of feather germ initiation, while others showed a lag between the histological appearance of feather germs and their macroscopic visualization. Thus, macroscopic observations do not accurately reflect the pattern of histogenesis.

Animals

MR imaging of susceptibility-induced magnetic field inhomogeneities.

A 90 degrees-tau 1-90 degrees-tau 2-image acquisition pulse sequence allows spatial mapping of resonant frequency. This sort of sequence has previously been used for magnet shimming, and its use in chemical-shift imaging has been proposed. The authors used this sequence in magnetic resonance imaging of a phantom to demonstrate the magnetic field gradients arising from susceptibility differences within the phantom and allow those gradients to be measured. Gradients may arise near interfaces between substances that cannot support the same magnetic flux density. The pulse sequence was found to work well in lower-field-strength instruments.

Brain

Multi-omics identification and functional validation of signal regulatory protein gamma as a prognostic biomarker and immune regulator in head and neck squamous cell carcinoma.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) comprises biologically diverse tumors, and durable responses to immune-checkpoint blockade are achieved by only a subset of patients. There remains a need for markers that connect clinical outcome with malignant-cell phenotypes and tissue-level immune organization. METHODS: We integrated The Cancer Genome Atlas HNSCC cohort (TCGA-HNSC), five Gene Expression Omnibus (GEO) validation cohorts, single-cell RNA sequencing, Visium spatial transcriptomics, cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq)-informed protein-potential inference, pharmacogenomic screening, genetic-risk analysis and experimental validation. A reconstructed 296-pipeline survival modelling framework was used to prioritize prognostic hub genes across validation-cohort-specific analyses. RESULTS: SIRPG was repeatedly ranked among the top ten selected genes in all five validation cohorts. At single-cell resolution, SIRPG-high tumor cells showed stronger malignant-cell features, immune-inhibitory and metabolic programs, Scissor-positive risk association, CLCA2/P53-related perturbation signals and inferred SIRPG-CD47/signal regulatory protein (SIRP) communication. Spatial analyses placed this axis within an immune-checkpoint-coupled niche, supported by Maxspin/multiview intercellular spatial modelling (MISTy) spatial coupling, communication analysis by optimal transport (COMMOT)-inferred CD47-SIRPG communication and scProTrans-inferred CD47/SIRPG protein-potential overlap. Functionally, SIRPG knockdown reduced HNSCC cell viability and increased apoptosis, whereas re-expression of short hairpin RNA (shRNA)-resistant SIRPG restored the CLCA2-BAX/BCL2 protein response. CONCLUSION: Together, these findings identify SIRPG as an immune-related prognostic hub and context-dependent tumor-cell regulator associated with apoptosis, immune communication and spatial microenvironmental organization in HNSCC.

Humans

Learning spatial dimensions with a visual sensory aid: Molyneux revisited.

The relationship between sensory aid research and several areas of perceptual learning has been explored with five experiments on learning the use of the Binaural Sensory Aid, an electronic sensor in which pitch specifies distance and interaural amplitude difference (IAD) specifies direction. The training task required reaching to objects in near space, with tactile error feedback. Perceptual learning for both dimensions was demonstrated within 72 trials, giving a level of performance comparable to the use of a natural sound source, although performance with the direction cue did not reach asymptote until a second training session. Training was unaffected by various kinds of regularity in the spatial target sequences, or by a reduction in the number of spatial target locations until only two locations were used; at this point directional accuracy declines. Training only one dimension at a time did not produce additional improvement of performance on that dimension, but did impair generalization of the direction cue. Learning of the pitch-distance dimension was generally better than that of the IAD dimension, possibly because of its greater discriminability with this device. Generally, the pattern of results indicates that in learning to use such devices subjects readily determine the sensory dimensions of the codes and have considerable ability to generalize to new locations.

Distance Perception

Amino acid sequence of ovine 6-phosphogluconate dehydrogenase.

The amino acid sequence of the NADP+-dependent enzyme ovine 6-phosphogluconate dehydrogenase has been determined by conventional direct protein sequence analysis of peptides resulting from digestion of the protein with trypsin and chemical cleavages with cyanogen bromide, hydroxylamine, and iodosobenzoic acid. The polypeptide contains 466 amino acids and its NH2 terminus is acetylated. The Candida utilis enzyme is inactivated by reaction of pyridoxal phosphate with two lysine residues (Minchiotti, L., Ronchi, S., and Rippa, M. (1981) Biochim. Biophys. Acta 657, 232-242). These residues are conserved in the ovine enzyme. In contrast to NAD+ dehydrogenases which have weakly related sequences and spatially related folds in their nucleotide-binding sites, no significant sequence homologies were detected between 6-phosphogluconate dehydrogenase and any of three other NADP+-requiring enzymes, glutamate dehydrogenase, p-hydroxybenzoate hydroxylase, and dihydrofolate reductase. This is in accord with structural data that show no spatial relationship between NADP+-binding sites in these enzymes.

Amino Acid Sequence

BISON: bi-clustering of spatial omics data with feature selection.

MOTIVATION: The advent of next-generation sequencing-based spatially resolved transcriptomics (SRT) techniques has reshaped genomic studies by enabling high-throughput gene expression profiling while preserving spatial and morphological context. Understanding gene functions and interactions in different spatial domains is crucial, as it can enhance our comprehension of biological mechanisms, such as cancer-immune interactions and cell differentiation in various regions. It is necessary to cluster tissue regions into distinct spatial domains and identify discriminating genes (DGs) that elucidate the clustering result, referred to as spatial domain-specific DGs. Existing methods for identifying these genes typically rely on a two-stage approach, which can lead to the phenomenon known as double-dipping. RESULTS: To address the challenge, we propose a unified Bayesian latent block model that simultaneously detects a list of DGs contributing to spatial domain identification while clustering these DGs and spatial locations. The efficacy of our proposed method is validated through a series of simulation experiments, and its capability to identify DGs is demonstrated through applications to benchmark SRT datasets. AVAILABILITY AND IMPLEMENTATION: The R/C++ implementation of BISON is available at https://github.com/new-zbc/BISON.

Software

The response of the strongly coupled AB system of citrate to typical 1H MRS localization sequences.

The response of the strongly coupled AB system of citrate to the STEAM and PRESS spatial localization sequences is developed analytically and then verified experimentally at 2.35 T. At this field strength, the response predicted by the complete strong-coupling calculation is shown to differ greatly from that of the simpler weak-coupling approximation. It is shown that the strong-coupling effects induce a significant field-strength dependence in the time-dependent modulations of the response to either sequence. These effects are illustrated for the STEAM and PRESS responses at field strengths of 1.5, 2.35, and 4.7 T. Independent of the chosen sequence, the increase in the signal-to-noise (S/N) of the frequency response with increasing field strength is shown to be significantly less for the citrate system than for uncoupled spins. The factors which weaken the S/N dependence of the citrate AB signal with increasing field strength are quantified and discussed.

Citrates

A simple way to look at DNA.

A method is presented for embedding nucleotide sequence data in a simple metric space. Computer graphical examination of spatially-represented sequences permits rapid searches for canonical patterns or interesting structures. Sequence comparisons are facilitated by plots of distance measures for homologous sequences, and the large-scale structure of the genetic code can be studied by measures such as fractal dimensionality.

Actins

Some factors affecting the perceived ordering of natural speech stimuli.

Primary auditory stream segregation--the perceptual segregation of acoustically related elements of a continuous auditory sequence into spatially distinct streams--disrupts recovery of the relative temporal order of repeated sequences of consonant and vowel syllables. Three experiments were performed to determine why the apparent temporal order of natural speech is not similarly disrupted. Exp. 1 (N =24) showed that the disruption is not dependent on repetition of the 32 experimental sequences of consonant and vowel syllables. Exps. 2 (N = 48) and 3 (N = 20) showed that when 4 English monosyllables are used as stimuli and syntactic and intonational structure is present then the temporal integrity of the acoustic signal is preserved perceptually. Despite accurate resolution of order for the 40 experimental sequences, errors of words were common. These errors often imposed a syntactic organization on the resulting sequence.

Auditory Perception

Identification of the calmodulin binding domain of alpha-fodrin and implications for folding.

A cDNA clone producing a protein that binds calmodulin has been isolated from a mouse macrophage library. The cDNA was sequenced and identified as coding for fodrin. By deleting part of the sequence, the calmodulin binding domain was located. The site is situated on repeat 11 of fodrin probably on its extra arm. This part of the sequence exhibits great similarity to other calmodulin binding proteins. Analysis of the sequence and spatial structure of calmodulin revealed a domain which is quite complementary to the sequence identified on fodrin. These results provide a new insight into the structure of fodrin and consequently into the structure of proteins of the spectrin family. A model for the general folding of these molecules is proposed, involving a simple three-layer folding. The structure was further corroborated by analysis of charge distribution in the vicinity of the calmodulin binding site. The folding we propose is in good agreement with digestion experiments and explains observations in diseases resulting from mutations of human spectrin.

Amino Acid Sequence

Hemispheric activation increases positive manifold for lateralized cognitive tasks: an extension of Stankov's hypothesis.

Stankov (1983a, Journal of Educational Psychology, 75, 471-490) suggests that the dual task paradigm, requiring the division of attention, increases positive manifold (i.e., positive intercorrelations) for cognitive tasks relative to the single task paradigm. Two dual task studies are reported. Unimanual finger-tapping served as the primary task and the short-term retention (20 sec) of digit or spatial-location sequences served as the secondary tasks. When both tasks were lateralized to the same hemisphere (digits and right-hand tapping or spatial locations and left-hand tapping), highest memory task intercorrelations (Experiment 1) and better retention of sequences (Experiments 1 and 2) resulted. Left-hand tapping produced more leftward looking and right-hand tapping more rightward looking (Experiment 2). Overflow from lateralized finger-tapping may shift the gradient of attentional activation toward the contralateral hemisphere, producing the homolateral gaze direction, the increase in positive manifold, and the better retention of sequences lateralized to that hemisphere.

Adult

Mechanisms of differential axial blockade in epidural and subarachnoid anesthesia.

The mechanisms of persistent differential blocks that accompany subarachnoid and epidural anesthesia are clarified here with the aid of two principles derived from in vitro study of individual myelinated axons: 1) conduction can leap two consecutive blocked nodes but not three, and 2) a fiber length with more than three consecutive nodes bathed by weak anesthetic may block by decremental conduction, the requisite concentration varying inversely with the number of nodes bathed by anesthetic. Principle 1 applies in epidural blockade, where anesthetic bathes only a few millimeters of segmental nerve extradurally in the intervertebral foramen. Here, three-node block will be rare in large, long-internode fibers but likely in small, short internode fibers, thus explaining the differential retention of motor power in the presence of block of pain, which is achieved in epidural anesthesia when relatively weak solutions are used, as in obstetrics. Principle 2 may intervene in subarachnoid blockade where, cephalad to the site of puncture, increasingly concentrated anesthetic bathes increasing lengths of fibers in the craniocaudal succession of spinal nerve roots. This will produce decremental conduction block in increasingly long internode fibers in successive roots, reflected in a corresponding craniocaudal segmental sequence of blocked physiological functions: vasoconstriction, cutaneous temperature discrimination, pinprick pain sensibility, and skeletal motor activity. The segmental spatial differential sequence migrates with time but resembles the temporal differential sequence of loss seen at the onset of peripheral nerve blocks. Several other previously disparate clinical observations follow logically from the new interpretation.

Anesthesia, Epidural

Integrating genomic and spatial analyses to describe tuberculosis transmission: a scoping review.

Tuberculosis remains a leading cause of infection-related mortality, and efforts to reduce its incidence have been hindered by an incomplete understanding of local Mycobacterium tuberculosis transmission dynamics. Advances in pathogen sequencing and spatial analysis have created new opportunities to map M tuberculosis transmission patterns more precisely. In this scoping review, we searched for studies combining pathogen genetics and location data to analyse the spatial patterns of M tuberculosis transmission and identified 142 studies published between 1994 and 2024. Secular changes in genetic methods were observed, with genome sequencing approaches largely replacing lower-resolution genotyping methods since 2020. The included studies addressed four primary research questions: how are tuberculosis cases and M tuberculosis transmission clusters geographically distributed; do spatially concentrated M tuberculosis clusters exist, and where are these areas located; when spatial concentration occurs, what host, pathogen, or environmental factors contribute to these patterns; and do identifiable relationships exist between the spatial proximity of tuberculosis cases and the genetic similarity of the M tuberculosis isolates infecting these individuals? Collectively, in this Review, we examined the available study data, evaluated the analytical requirements for addressing these questions, and discussed opportunities and challenges for future research. We found that the integration of spatial and genomic data can inform a detailed understanding of local M tuberculosis transmission patterns, but improved study designs and new analytical methods to address gaps in sampling completeness and to integrate additional movement data are needed to fully realise the potential of these tools.

Humans

Spatial organization of repetitive DNA sequences in the bovine sperm nucleus.

During spermatogenesis, DNA in the sperm head becomes more tightly condensed as histones are replaced by protamine-like molecules. In this article, the question is asked whether, during the production of this highly differentiated cell, controls are imposed on the spatial organization of DNA within the nucleus. Heads from bull spermatozoa were isolated by a technique that removed the plasma membrane and acrosomal contents, and the DNA was induced to decondense by addition of 2-mercaptoethanol and trypsin. Under these conditions, decondensation was induced in all regions of the head. To determine whether there was any spatial restraint on packaging of the genome, three DNA probes were used (pl.709-512, containing an interspersed repetitive sequence; pCSIH, containing a copy of the major bovine centromeric statellite sequence; p18 s and p28 s, containing the 18 S and 28 S ribosomal genes) that might be expected to hybridize to different regions. Results showed that the interspersed repetitive probe hybridized to all regions of the head, whereas the ribosomal and centromeric probes hybridized to sequences that were largely confined to the equatorial region of the sperm. We conclude that organization of the genome in the bovine sperm nucleus is not random.

Animals

Temporal and spatial aspects of lingual coarticulation in /kl/ sequences: a cross-linguistic investigation.

Temporal and spatial aspects of lingual coarticulation in /kl/ clusters in intervocalic position (VklV) were investigated in six European languages: Catalan, English, French, German, Italian, and Swedish. Three speakers of each language repeated a set of real words and nonsense items five times. Temporal overlap of /k/ and /l/ gestures, as represented by a numerical "overlap index", was interpreted as tongue-tip/tongue-body coarticulation, and was measured from electropalatographic and airflow records. Results revealed several language-specific features. For example, the tendency to overlap was different for the six languages. All the languages except Swedish showed some instances of overlap, and Catalan showed the strongest tendency. The vowel environment also had a significant effect: The presence of an open back vowel in V1 and V2 positions increased the tendency for overlap to occur. However, there was no statistically significant difference in overlap between nonsense and real words. Spatial information from EPG data showed that articulatory placement of the tongue-body gesture was more retracted in a /kl/ cluster compared to a singleton consonant. All the languages under investigation showed this phenomenon. These findings are discussed in terms of possible constraints operating between the tip/blade and tongue-body systems.

Female

Optimized ultra-fast imaging sequence (OUFIS).

The DUFIS sequence can make ultra-fast images (approximately 10 ms) without the use of rapidly switched gradients. The RF excitation sequence is spatially selective so that only a small fraction of the magnetization in each imaging pixel is used which produces a poor imaging signal to noise ratio (SNR). We have developed several alternative RF sequences that use RF pulses with multiple phases, and also with just 0 degrees and 180 degrees phases to excite almost all the magnetization in a pixel and greatly improve the SNR. The optimization of these pulse sequences (now called OUFIS) have been conducted both analytically and by numerical searches, with various linear and nonlinear models. Both theoretical and computational methods used in the optimizations are described in detail. Preliminary experimental results are briefly presented with several possible applications of the OUFIS excitation sequences suggested.

Algorithms